PK/Efficacy Bridging Study of ASTX727 in Chinese Subjects with Myelodysplastic Syndromes
- Conditions
- Myelodysplastic Syndromes
- Interventions
- Registration Number
- NCT06091267
- Lead Sponsor
- Otsuka Beijing Research Institute
- Brief Summary
This is an Open-Label, Crossover, Pharmacokinetic and Efficacy Bridging Study of Oral ASTX727 versus IV Decitabine in Chinese Subjects with Myelodysplastic Syndromes
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 72
- Agree to participate in this trial and voluntarily sign the informed consent form.
- Men or women ≥ 18 years at the time of signing the informed consent form.
- Subjects with MDS previously treated or untreated with de novo or secondary MDS.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening.
- Prior treatment with more than 1 cycle of azacitidine or decitabine.
- Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment.
- Conditions as judged by the investigator to be inappropriate for participation in the clinical trial.
- Previous diagnosis of malignant tumor.
- History of immune deficiency.
- Acute myeloid leukemia (AML) with bone marrow or peripheral blast count ≥ 20% or other malignant hematological diseases.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description ASTX727 and IV Decitabine IV Decitabine Cycle1：ASTX727 tablets, oral, 1 tablet/day for 5 days；Cycle2：IV Decitabine, 20 mg/m\^2, is administered for 1 hour at a time for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days ASTX727 and IV Decitabine only Decitabine and cedazuridine Cycle1：ASTX727 tablets, oral, 1 tablet/day for 5 days；Cycle2：IV Decitabine, 20 mg/m\^2, is administered for 1 hour at a time for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days IV Decitabine and ASTX727 only Decitabine and cedazuridine Cycle1：IV Decitabine, 20 mg/m\^2, is administered for 1 hour at a time for 5 days； Cycle2：ASTX727 tablets, oral, 1 tablet/day for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days ASTX727 only Decitabine and cedazuridine ASTX727 tablets, oral, 1 tablet/day for 5 days； ASTX727 and IV Decitabine Decitabine and cedazuridine Cycle1：ASTX727 tablets, oral, 1 tablet/day for 5 days；Cycle2：IV Decitabine, 20 mg/m\^2, is administered for 1 hour at a time for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days IV Decitabine and ASTX727 Decitabine and cedazuridine Cycle1：IV Decitabine, 20 mg/m\^2, is administered for 1 hour at a time for 5 days； Cycle2：ASTX727 tablets, oral, 1 tablet/day for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days IV Decitabine and ASTX727 IV Decitabine Cycle1：IV Decitabine, 20 mg/m\^2, is administered for 1 hour at a time for 5 days； Cycle2：ASTX727 tablets, oral, 1 tablet/day for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days
- Primary Outcome Measures
Name Time Method Complete Response Rate An analysis is planned when the last enrolled patient have completed Follow-up 12 months. Assess efficacy \[Complete Response Rate (CR)\] of treatment with ASTX727 in Chinese subjects with myelodysplastic syndromes (MDS);
5day_AUC0-τ An analysis is planned when the last enrolled patient have completed the treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 day. Assess pharmacokinetic (PK) parameters (Total 5-day AUC exposures of decitabine) after treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 days;
- Secondary Outcome Measures
Name Time Method Overall survival through study completion, an average of 1 year. Overall survival (OS).
Rate of transfusion independence through study completion, an average of 1 year. Rate of transfusion independence: The proportion of subjects who had no blood transfusion of 2 or more units of PRBCs for 56 days or more after treatment;
disease progression through study completion, an average of 1 year. Time to progression to acute myeloid leukemia (AML);
Rac_AUC0-τ through study completion, an average of 1 year. PK parameters of E7727 and E7727-epimer: accumulation ratio based on AUC0-τ.
Clinical Response Rate through study completion, an average of 1 year. Clinical Response Rate: The proportion of subjects who achieve CR, PR, marrow complete response (mCR), and hematologic improvement (HI) based on IWG 2006 criteria.
peak concentration (Cmax) through study completion, an average of 1 year. Decitabine PK parameters: peak concentration (Cmax).
accumulation ratio based on AUC0-τ (Rac_AUC0-τ). through study completion, an average of 1 year. Decitabine PK parameters: accumulation ratio based on AUC0-τ (Rac_AUC0-τ).
Cmax through study completion, an average of 1 year. PK parameters of E7727 and E7727-epimer: Cmax.
Objective Response Rate through study completion, an average of 1 year. Objective Response Rate (ORR): The proportion of subjects who achieve CR and partial response (PR) based on IWG 2006 criteria;
time to peak concentration (Tmax) through study completion, an average of 1 year. Decitabine PK parameters: time to peak concentration (Tmax).
area under the plasma concentration-time curve over a dosing interval (AUC0-τ). through study completion, an average of 1 year. Decitabine PK parameters: area under the plasma concentration-time curve over a dosing interval (AUC0-τ).
accumulation ratio based on Cmax (Rac_Cmax). through study completion, an average of 1 year. Decitabine PK parameters: accumulation ratio based on Cmax (Rac_Cmax).
Tmax through study completion, an average of 1 year. PK parameters of E7727 and E7727-epimer: Tmax.
Rac_Cmax through study completion, an average of 1 year. PK parameters of E7727 and E7727-epimer: accumulation ratio based on Cmax.
Safety assessment through study completion, an average of 1 year. Safety as assessed by adverse events (AEs), concomitant medications, physical examination, clinical laboratory tests (hematology , serum chemistry and urinalysis), vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and electrocardiogram (ECG).
AUC0-τ through study completion, an average of 1 year. PK parameters of E7727 and E7727-epimer: area under the plasma concentration-time curve over a dosing interval .
Trial Locations
- Locations (1)
The First Affiliated Hospital,Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China